What are the possible causes of long-term intermittent midfoot pain in a 71-year-old man with a history of reactive arthritis and HLA-B27 (Human Leukocyte Antigen B27) positivity, worsened by exercise?

Differential Diagnosis of Intermittent Midfoot Pain in HLA-B27 Positive Patient with Reactive Arthritis History

The most likely cause is recurrent or chronic spondyloarthritis-related peripheral arthritis affecting the midfoot, given the patient's HLA-B27 positivity and reactive arthritis history, though peripheral artery disease and degenerative foot arthritis must also be considered in this age group. 1

Primary Diagnostic Considerations

Spondyloarthritis-Related Peripheral Arthritis

• HLA-B27 positivity significantly increases the likelihood of peripheral spondyloarthritis manifestations, including foot involvement, even in patients with a prior reactive arthritis diagnosis 1
• The intermittent nature, exercise-induced worsening, and bilateral (though asymmetric) presentation are consistent with spondyloarthritis patterns 1
• HLA-B27 positive patients with reactive arthritis can develop chronic or recurrent inflammatory arthritis, with the antigen associated with accelerated joint destruction and more severe disease evolution 2
• The absence of visible swelling does not exclude inflammatory arthritis, as deep midfoot inflammation may not produce obvious external signs 1

Peripheral Artery Disease (PAD)

• At age 71, PAD must be considered as foot/ankle pain worsened by exercise is a recognized presentation of lower extremity ischemia 1
• However, PAD-related foot pain typically presents as aching discomfort that may be present at rest and is not quickly relieved, which differs from this patient's day-or-two duration pattern 1
• The bilateral nature and lack of other vascular findings (hair loss, nail changes, pulse abnormalities) make PAD less likely as the primary cause 1

Degenerative Foot Arthritis

• Foot/ankle arthritis presents as aching pain after variable degrees of exercise and may not be quickly relieved by rest 1
• The intermittent pattern lasting 1-2 days is somewhat atypical for pure degenerative disease, which tends to be more constant 1
• Age 71 makes degenerative changes likely as a contributing factor, though probably not the sole explanation 1

Recommended Diagnostic Approach

Clinical Assessment

• Document inflammatory features: morning stiffness duration, night pain, improvement with activity versus rest, and any associated heel pain (enthesitis) 1
• Examine for enthesitis at Achilles insertion and plantar fascia, which are common spondyloarthritis manifestations often accompanying midfoot involvement 1
• Assess lower extremity pulses (dorsalis pedis, posterior tibial) to evaluate for PAD 1
• Look for other spondyloarthritis features: back pain with inflammatory characteristics, buttock pain, or other joint involvement 1

Initial Imaging

• Plain radiographs of both feet are the appropriate first-line imaging, looking for erosions, joint space narrowing, or periostitis characteristic of spondyloarthritis 1
• If radiographs are negative but clinical suspicion for spondyloarthritis remains high, MRI of the affected foot can detect bone marrow edema and synovitis before radiographic changes appear 1
• Consider sacroiliac joint imaging if not previously performed, as axial involvement may coexist 1

Laboratory Testing

• Inflammatory markers (ESR, CRP) should be checked, though normal values do not exclude spondyloarthritis 3
• The HLA-B27 status is already known (positive), which increases pretest probability but does not confirm active disease 3

Critical Clinical Pitfalls

• Do not dismiss the diagnosis of active spondyloarthritis based solely on the absence of visible swelling or normal inflammatory markers 3
• The history of "reactive arthritis" does not mean the disease has resolved; HLA-B27 positive reactive arthritis can evolve into chronic spondyloarthritis with peripheral manifestations 2, 4
• Midfoot involvement is a recognized pattern in spondyloarthritis and should not be confused with more common forefoot (metatarsophalangeal) involvement seen in rheumatoid arthritis 1
• In this age group, multiple pathologies may coexist—inflammatory arthritis and degenerative changes can occur simultaneously 1

When to Refer to Rheumatology

Referral to rheumatology is warranted given the combination of HLA-B27 positivity, prior reactive arthritis, and recurrent inflammatory-pattern joint symptoms 3. The rheumatologist can determine if this represents chronic spondyloarthritis requiring disease-modifying therapy versus episodic reactive phenomena.